Otitis media with effusion (OME) is one of the largest public health problems of young children. The inflammatory events in OME lead to effusion and tissue hyperplasia, producing temporary or permanent hearing loss. Immune responses play a major role in OME, since immunity is intimately involved in the host response to infection of the middle ear (ME). Inflammatory events based upon response to antigen have also been implicated in OME pathogenesis. Issues to be studied in the present application include whether immune response to bacterial antigens prolongs OME after antibiotic treatment. We will also investigate whether antibiotic treatment of bacterial OME decreases the sensitization of immunity by reducing the level and duration of bacterial antigens present in the ME. The cellular and molecular mechanisms which control immune responses in the ME will be studied, with a goal of determining whether ME immunity and resistance to infection can be increased, and immune-mediated inflammation can be decreased. Finally, we will study the contributions of growth factors in generating ME tissue hyperplasia during OME. We will identify substances that promote tissue proliferation and differentiation, and which are present in the ME during OME. We will also investigate the response of the ME mucosa to direct application of growth factors.